When American astrophysicist Neil deGrasse Tyson said that “we are, each of us, a little universe”, he was referring to the myriad of atoms, molecules and dynamic chemical reactions that make up the human body. For example, a peek just below the skin, reveals numerous immune cells keenly keeping watch for potentially dangerous invaders.
Sometimes, however, these immune guardians can backfire. T cells, usually activated by antigen-presenting immune cells called dendritic cells (DCs) to produce inflammatory factors in response to invaders, can be overactive and result in chronic inflammatory skin conditions such as eczema and psoriasis.
“Antigen-presenting cells are essential for T cell activation, but their classification and function in skin is not clearly understood,” explained Kenji Kabashima, Senior Principal Investigator at the A*STAR Skin Research Labs (A*SRL), adding that within this vast, unexplored universe lies potential drug targets to calm chronic skin flare-ups.
Kabashima and his team took on the challenge of mapping DCs in healthy and inflamed skin, one cell at a time. First, they collected skin samples from patients with inflammatory skin conditions and classified DCs and other immune cells individually using flow cytometry. They then employed cutting-edge single-cell sequencing technology to decode the RNA signatures in these cells.
The researchers’ efforts culminated in the first-ever comprehensive database of skin DCs, which includes the molecular profiles of healthy cells as well as those involved in inflammatory skin diseases.
“The single-cell universe of DCs is a new classification scheme of antigen-presenting cells based on single-cell-level analysis,” said Satoshi Nakamizo, first author of the study, adding that these new classifications provide a more holistic understanding of connections between dendritic cell function and their roles in chronic disease.
As part of the team’s analysis, the scientists uncovered a novel dendritic cell subtype called CD14+ DC3. These cells produce the immune-activating proteins IL1B and IL23A, both of which are known triggers of the red and scaly patches associated with psoriasis.
Nakamizo said that the study identifies CD14+ DC3s as a new potentially druggable target to treat psoriasis, dermatitis and other inflammatory skin conditions. However, this dataset is just the tip of the iceberg. According to Kabashima, future single-cell sequencing efforts will focus on understanding where DCs lie within the complex skin architecture and how they interact with other skin cells.
“In addition, similar analyses are currently underway for skin diseases other than atopic dermatitis and psoriasis,” concluded Kabashima.
The A*STAR-affiliated researchers contributing to this research are from the A*STAR Skin Research Labs (A*SRL) and Singapore Immunology Network (SIgN).